RAIG1 is a novel p53-regulated and growth-proliferative gene in human tumors

2540 Retinoic acid-inducible gene 1 (RAIG1), an orphan G protein-coupled receptor, was identified using differential display as induced by retinoic acid in the squamous carcinoma cell line UMSCC-22B (Cheng, Y. and Lotan, R, J. Biol. Chem., 273(52), 35008-35015, 1998). Using hierarchical cluster analysis of microarray data from breast tumor cell lines, we find that RAIG1 is classified in the cell proliferation cluster, suggesting its potential role in tumor growth. RAIG1 is expressed in G1 phase of the cell cycle in a cell-cycle-dependent manner. Taqman analysis of RAIG1 gene expression in a RNA tumor cell line panel indicated that it is over-expressed in lung, breast, colorectal, ovarian and pancreatic tumor cells. Interestingly, we observed that the expression of RAIG1 was repressed in human ovarian cancer cells at the onset of apoptosis induced by p53. There are 4 putative p53 DNA binding sites in the promoter of the RAIG1 gene. Chromatin immunoprecipitation analysis indicated that p53 binds to the promoter of RAIG1 in vivo, suggesting p53 may directly repress its expression. Moreover, the expression of RAIG1 in NIH/3T3 cells caused ligand-independent transformation and knock-down of RAIG1 gene expression in AsPc-1 pancreatic tumor cells by gene specific small-interfering RNA induced morphological change, suggesting its potential oncogenicity. Taken together, these data suggest a role for RAIG1 in tumor growth and progression.